No abstract

Sera from patients suffering from systemic autoimmune diseases such as systemic lupus erythematosus (SLE) and systemic sclerosis (SSc) have been shown to contain reactivities to nuclear components. Autoantibodies specifically targeting nucleolar antigens are found most frequently in patients suffering from SSc or SSc overlap syndromes. We determined the prevalence and clinical significance of autoantibodies directed to nucleolar RNA-protein complexes, the so-called small nucleolar ribonucleoprotein complexes (snoRNPs). A total of 172 patient sera with antinucleolar antibodies were analysed by immunoprecipitation. From 100 of these patients clinical information was obtained by chart review. Autoantibodies directed to snoRNPs were detected not only in patients suffering from SSc and primary Raynaud's phenomenon (RP), but also in patients suffering from SLE, rheumatoid arthritis (RA) and myositis (PM/DM). Antibodies against box C/D small snoRNPs can be subdivided in antifibrillarin positive and antifibrillarin negative reactivity. Antifibrillarin-positive patient sera were associated with a poor prognosis in comparison with antifibrillarin negative (reactivity with U3 or U8 snoRNP only) patient sera. Anti-Th/To autoantibodies were associated with SSc, primary RP and SLE and were found predominantly in patients suffering from decreased co-diffusion and oesophagus motility and xerophthalmia. For the first time autoantibodies that recognize box H/ACA snoRNPs are described, identifying this class of snoRNPs as a novel autoantigenic activity. Taken together, our data show that antinucleolar patient sera directed to small nucleolar ribonucleoprotein complexes are found frequently in other diseases than SSc and that categorization of diagnoses and clinical manifestations based on autoantibody profiles seems particularly informative in patient sera recognizing box C/D snoRNPs.

Using the immunoblotting technique, sera from 433 patients with rheumatic diseases were screened for the presence of antibodies against several nuclear and cytoplasmic antigens, such as RNP, Sm, Ro(SSA), La(SSB), CR-19 (centromeric antigen), Topo-1 (Scl-70), Jo-1, histone and 56 kD. At the same time clinical data from these patients were collected without prior knowledge of the immunoblotting results. Syndrome-specific autoantibodies were found for mixed connective tissue disease (antibodies against the RNP related 70 kD antigen), for CREST (anti-CR-19 antibodies), for diffuse scleroderma (anti-Topo-1 antibodies) and for polymyositis (anti-Jo-1 antibodies). Almost all specific autoantibodies were present exclusively in patients with a connective tissue disease. Controls were only in a few cases positive for antihistone and anti-56 kD antibodies. Associations of specific autoantibodies with clinical and laboratory features of the patients were mostly as expected. However, some unexpected associations were found, for example polymyositis and calcinosis with anti-Sm antibodies, sicca symptoms with anti-centromere antibodies and leucopenia with Ro(SSA) and La(SSB).

Objective. To evaluate correlations between changes in a n t i 4 1 RNA antibody levels and disease activity in 9 patients with systemic lupus erythematosus (SLE) overlap syndrome who were prospectively followed up for at least 3 years.Methods. Anti-U1 RNA antibody levels were measured quantitatively, using a nitrocellulose filter binding assay. Disease activity was measured with a validated SLE activity index.Results. All 9 major disease exacerbations were associated with peaks in a n t i 4 1 RNA antibody level.Conclusion. These results seem to indicate that measuring a n t i 4 1 RNA antibody levels can be useful for monitoring disease activity.Sera from patients with connective tissue diseases often contain antibodies against proteins present in small nuclear ribonucleoprotein (snRNP) particles (1). These snRNPs contain a uridine-rich RNA and

Sera of 34 patients with progressive systemic sclerosis and of 11 patients with polymyositis/dermatomyositis (PM/DM) were analyzed by the immunoblotting technique for the presence of marker antibodies. The presence of anti-centromere, anti-Topoisomerase-I (anti-Topo-I) and anti-Jo-1 antibodies was found to be highly specific for the CREST syndrome, diffuse scleroderma and PM/DM, respectively, but only of limited sensitivity (78, 44 and 45%, respectively). Anti-Topo-I positive diffuse scleroderma patients had a more severe disease (digital pitting scars and renal insufficiency) than anti-Topo-I negative diffuse scleroderma patients. Anti-Jo-1 was associated with interstitial lung disease. Longitudinal studies showed a constant antibody pattern. Our results confirm the clinical usefulness of these marker antibodies.